Bilateral testicular infiltration as the initial presentation of NRAS-mutant juvenile myelomonocytic leukemia: rapid molecular remission following azacitidine and haploidentical stem cell transplantation.

BACKGROUND

Juvenile myelomonocytic leukemia (JMML) rarely manifests with extramedullary involvement beyond spleen, liver, or skin; testicular infiltration at diagnosis is unreported. We describe a Novel Case of bilateral testicular leukemic infiltration as the initial presentation of NRAS-mutant JMML in a toddler, with rapid remission following azacitidine bridging and haploidentical HSCT.

CASE PRESENTATION: A 2-year-old boy presented with pallor, abdominal distension, and bilateral scrotal swelling. Labs: leukocytosis (58 × 10⁹/L, monocytes 12.8 × 10⁹/L), anemia (Hb 8.2 g/dL), HbF 22%. BM confirmed JMML with NRAS p.G12D (VAF 42%). No pathogenic variants were detected in KRAS, PTPN11, CBL, or NF1. Conventional cytogenetic analysis demonstrated a normal male karyotype (46,XY). US: testes enlarged (18.8/18.2 mL) with hypoechoic infiltration. Azacitidine (75 mg/m²/d × 5, 2 cycles) reduced counts and size. Paternal haplo-HSCT (Flu-Treo-TT conditioning, PTCy) engrafted D + 18; testes normal at 6 weeks, molecular remission (NRAS-) at 3 months.

CONCLUSIONS

This novel case underscores the efficacy of azacitidine and haploidentical HSCT for NRAS-mutant JMML with testicular involvement. Routine genital examination and ultrasound are recommended for male patients.